The value of oral microbiome therapy for recurrent C. difficile infection

A disrupted gastrointestinal microbiome is often the basis of Clostridioides difficile infection. SER-109 is an oral microbiome therapeutic containing live Firmicutes bacterial spores and was designed to prevent recurrence of C. difficile infection.

ECOSPOR III was a double-blind Phase 3 superiority trial of SER-109 vs. placebo in patients with recurrent C. difficile infection. Adult patients with C. difficile infection who had at least three other episodes in the preceding 12 months and who had responded to standard of care antibiotic therapy were randomized to receive either SER-109 or a matching placebo once daily over a three-day period. The results were reported in the New England Journal of Medicine.

The study was cut short due to the COVID pandemic after the enrollment of 182 patients, 89 in the SER-109 arm and 93 in the placebo arm. At the 8-week primary efficacy point, patients in the SER-109 arm had a significantly lower C. difficile infection recurrence rate compared to patients in the placebo arm (12% vs. 40%; relative risk, 0.32; 95% confidence interval, 0.18-0.58). Sustained clinical response at 8 weeks was also higher with SER-109 compared to placebo (88% vs. 60%). Stratified analysis by age and treatment antibiotic was performed. Clinical response was in favor of SER-109 across both age groups (< 65 years and ³ 65 years) and both treatment antibiotics (vancomycin and fidaxomicin). However, the stratified analysis was less powered due to the small number of patients in some strata. A safety analysis did not reveal any significant adverse events related to the investigational agent. The results of microbiome analysis showed engraftment of Firmicutes bacteria by the first week, persisting through the eighth week. Stool specimens of patients in the SER-109 arm had bile-acid profiles that are known to inhibit C. difficile spore germination.

SER-109 appears to be effective and safe in preventing C. difficile recurrence, based on these study findings.

(Feuerstadt et al. N Engl J Med. 2022; 386:220-229.)